This equipment grant is requesting funds for the purchase of an isothermal titration microcalorimeter (ITC) for the determination of ligand receptor dissociation constants and thermodynamic parameters by a group of very productive NIH-funded researchers in chemistry, medicinal chemistry, biochemistry, molecular biology, and biophysics. These investigators are involved in NIH funded research that deals either with the design and synthesis of small molecules for potential drug targets or the utilization of small molecule ligands to study biological processes associated with various diseases. Their research addresses such diverse areas as male contraceptives, tuberculosis, anthrax, heart failure, cancer, carcinogenesis, and HIV. Presently, there is no available ITC instrument at the University of Minnesota-Twin Cities campus, which is a leader nationally in biomedical research. Many inhibitors derive their affinity by non- specific entropic interactions (i.e. desolvation) rater than specific hydrogen-bonding and van der Waal interactions that is manifested in the enthalpy. Thus, knowledge of the relative thermodynamic signature is vitally important. The Institute of Therapeutics and Drug Discovery (ITDD) will maintain the instrument and provide user training of the ITC, which will be paid for by the Department of Medicinal Chemistry.